Leveraging AI for validating the association between minimal residual disease (MRD) and survival outcomes in multiple myeloma.

Abstract

7547 Background: Minimal residual disease (MRD) has been recently accepted by the Food and Drug Administration (FDA) as an endpoint for accelerated approval in Multiple Myeloma. However, emerging data from recent trials were not included in previous analyses. While literature-based meta-analyses on the correlation between MRD and approved clinical outcomes typically require extensive manual review, leveraging AI with expert-in-the-loop validation can efficiently generate reliable evidence from comprehensive clinical studies with up-to-date outcomes. Methods: An AI-assisted framework was developed to identify relevant studies and extract critical information via two independent objectives. The first objective examined trial-level associations, modeling treatment effects on MRD and clinical endpoints across patient populations using weighted least squares, with association strength measured by coefficients of determination (R²) and 95% confidence intervals (CIs). The second objective analyzed individual-level associations using synthetic individual patient data (SynthIPD) generated from the published Kaplan-Meier plots and summary statistics of patient subgroups. Results: AI-assisted screening identified eligible studies (>50 patients per treatment arm) reporting progression-free survival (PFS), overall survival (OS), and MRD-negative complete response rates (MRD-CR rate) using multi-parameter next-generation flow cytometry or sequencing methods (sensitivity threshold ≥10⁻⁵), expanding previous analyses from 15 to 20 two-arm studies. Trial-level analysis demonstrated an R² of 0.69 (95% CI 0.50–0.89) for PFS log hazard ratio versus MRD-CR rate log odds ratio. Analysis of synthetic individual data from Kaplan-Meier curves using a novel digitization method yielded a global odds ratio of 7.28 (95% CI 5.60–8.95) for individual-level correlation between MRD-CR rates and PFS outcomes. Conclusions: This study validates MRD-CR rate as an endpoint for accelerated approval in MM through rapid AI-assisted literature review and synthetic individual patient data. The findings demonstrate moderate correlation between MRD-CR rate and median PFS at both trial and individual levels, consistent with previous literature but incorporating additional eligible studies. The novel SynthIPD approach presents an efficient alternative to traditional data-sharing methods while maintaining analytical robustness. These results align with current Oncologic Drugs Advisory Committee (ODAC) surrogacy analysis methods and support the utility of MRD assessment in MM clinical trials.